The biochemical response of living cells to external stimuli is the focus of active current research. Current methods known in the art usually involve the introduction of modified nucleotides or proteins into the cell. The modified nucleotides or proteins interact with the analytes of interest in the cell to produce an externally-detectable signal, such as a fluorescent signal from green fluorescent protein (GFP) or an activatable label such as a molecular beacon. These methods require that the cell of interest be chemically modified before it can be studied. No currently-known method allows an arbitrary analyte of interest to be monitored in an unmodified living cell.
Moreover, existing methods are typically integrating methods, in that they can monitor the build-up of an analyte of interest. This means that existing methods cannot monitor fluctuations in the concentration of the analyte of interest in real time. What is needed is the ability to measure in real time fluctuation in the concentration of an analyte of interest inside an unmodified living cell.